1. Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University

2. BJ Casey, Ph.D., Sackler Professor and Director Sackler Institute for Developmental Psychobiology Weill Medical College of Cornell University Insights into the Developing Brain from Functional Neuroimaging Studies

3. Key Points 1)Examine developmental progressions in terms of transitions into and out of stages of development rather than single snap shot in time; 2)Examine individual differences within a developmental stage in terms of potential risk and/or resilience factors.

4. Immature cognition is characterized by greater susceptibility to interference Ability to suppress inappropriate thoughts and actions in favor of appropriate ones (cognitive control), especially in. the context of emotion or incentives. Casey et al. 2000, 2002, 2005a, b,c

5. Overarching Question How is the brain changing during development that may explain behavioral changes, especially nonlinear ones?

6. Dramatic developmental changes in prefrontal and subcortical regions during adolescence Subcortical regions including limbic (accubens) regions (Sowell et al, 1999) Focus has typically been on prefrontal cortex (PFC) Sowell et al 1999 Nature Neuroscience

7. Functional Maturation Adolescence Prefrontal Cortex Protracted Development of Prefrontal Control Regions Earlier Development of Subcortical Limbic Regions

8. Functional Maturation Adolescence accumbens Prefrontal Cortex Protracted Development of Prefrontal Control Regions Earlier Development of Subcortical Limbic Regions

9. Thirty-seven participants 12 adults (mean age:25 years; 6 female) 12 adolescents (mean age:16 years; 6 female) 13 children (mean age: 9 years; 7 female) Reward = = Cue = Assessment of Developmental Differences in Response to Rewarding Events

15. Participants are faster on trials that give the largest reward.

16. * * Imaging Results Adolescents are similar to adults in volume of accumbens activity BUT similar to children in prefrontal activity.

17. -2 0 1 2 3 4 Protracted development of the OFC relative to the accumbens Normalized Extent of Activity Age in years Galvan et al 2006 J Neuroscience 5 10 15 20 25

18. Neural recruitment differs by region for age groups and corresponds to enhanced activity in the accumbens in adolescents. 0 200 400 600 800 1000 Nucleus Accumbens Orbital Frontal Cortex No of Interpolated Voxels (mm3) * 0 0.1 0.2 0.3 0.4 Nucleus AccumbensOrbital Frontal Cortex Peak % MR Signal Change * * * * Volume of Activity Children Adolescents Adults

19. -Differential development of subcortical relative to prefrontal control regions may explain increased engagement in high risk, incentive driven behaviors. Rate of Maturation Adolescence Different Developmental Trajectories accumbens/amygdala prefrontal cortex

20. 0 1 2 51015202530 Age (years) % MR Signal Change Individual variability in accumbens activity across development

21. Accumbens activity is correlated with risky behavior Galvan et al 2006 Developmental Science

22. Differential development of limbic subcortical vs. cortical control regions may be related to increased risking taking behavior in adolescence. Individual differences in tendency to engage in risky behavior may compound risk for poor outcomes during this developmental period. Impulsive and risky behavior Rate of Maturation Adolescence accumbens prefrontal cortex

23. Functional Maturation Adolescence amygdala Prefrontal Cortex Protracted Development of Prefrontal Control Regions Earlier Development of Subcortical Limbic Regions

24. 500 ms Emotional Go/Nogo Task 500 ms 2000 - 14,500 ms Hare et al 2005 Bio Psychiatry

25. 10 15 20 25 30 Enhanced activity in amygdala in adolescents relative to children & adults when approaching negative information Age in Years

26. Emotional Reactivity to Empty Threat: initial reactivity versus sustained reactivity earlymiddlelate Early Trials Middle Trials Late Trials

27. Emotional Reactivity to Empty Threat: initial reactivity versus sustained reactivity earlymiddlelate Early Trials Middle Trials Late Trials

28. Emotional Reactivity to Empty Threat: initial reactivity versus sustained reactivity earlymiddlelate Early Trials Middle Trials Late Trials

29. Sustained amygdala activity (late - early trials) Habituation of Amygdala Response to empty threat related to Trait Anxiety (i.e., decrease in activity from early to late trials) Trait Anxiety Score

30. Anxious Individual Less Anxious

31. Functional Connectivity Between Prefrontal Regions and Amygdala is associated with Habituation of Amygdala Response

32. Differential development of subcortical limbic regions relative to prefrontal control regions during adolescence are paralleled by changes in behavior. Individual differences in responses to positive or negative events, together with these developmental changes may put certain teens at risk for poor outcomes. Maturation Adolescence Conclusions accumbens/amygdala prefrontal cortex